The present invention relates to collagen containing sponges for improved sustained release delivery of pharmaceuticals.
Collagen has been used previously as a component in pharmaceutical sponges. Artandi (U.S. Pat. No. 3,157,524, issued Nov. 17, 1964), disclosed a sponge comprised of acid treated swollen collagen. Oluwasanmi et al. (J. Trauma 16:348-353 (1976)) disclosed a 1.7 millimeter thick collagen sponge that is crosslinked by glutaraldehyde. Collins et al. (Surg. Forum 27:551-553 (1976)) disclosed an acid-swollen collagen sponge that is crosslinked by glutaraldehyde. Berg et al. (U.S. Pat. No. 4,320,201, issued Mar. 16, 1982), disclosed a swollen sponge of high collagen purity produced by enzymatically degrading animal hides, digesting the mass in alkali or acid, mechanically comminuting the mass to produce specified lengths of collagen fibers, and crosslinking the fibers. Berg et al. (U.S. Pat. No. 4,837,285, issued Jun. 6, 1989), disclosed porous beads that have a collagen skeleton of 1 to 30 percent of the bead volume. These beads are useful as substrates for cell growth. Doillon et al. (Scanning Electron Microscopy III:1313-1320 (1984)), Doillon and Silver (Biomaterials 7:3-8 (1986)), and Doillon et al. (Biomaterials 8:195-200 (1987)), disclosed the growth of cells in collagen sponges with pore sizes of from about 60 to 250 .mu.m. Some of the sponges also contained hyaluronic acid and/or fibronectin. In addition, collagen has been used as a component in salves (PCT Patent Application WO 86/03122, published Jun. 5, 1986). Collagen has also been used for wound healing in conjunction with electrical currents (Silver and Dunn, U.S. Pat. No. 4,937,323, issued Jun. 26, 1990).
In addition, membranes containing collagen have been used in the prior art. Abbenhaus et al., Surg. Forum 16:477-478 (1965) disclosed collagen films of two to three millimeter thickness that were produced by heating and dehydrating collagen extracted from cow hides. Chu disclosed non-chemically crosslinked collagen implants produced by compression, which are useful for sustained drug delivery (European Patent Application 187014, published Jul. 9, 1986; U.S. Pat. No. 4,600,533, issued Jul. 15, 1986; U.S. Pat. No. 4,655,980, issued Apr. 7, 1987; U.S. Pat. No. 4,689,399, issued August 25, 1987; and PCT Patent Application WO 90/00060, published Jun. 28, 1989). Cioca (U.S. Pat. No. 4,412,947, issued Nov. 1, 1983), disclosed an essentially pure collagen sheet made by freeze drying a suspension of collagen in an organic acid. Kuroyanagai et al. (European Patent Application 167828, published Jan. 15, 1984; U.S. Pat. No. 4,642,118, issued Feb. 10, 1987), disclosed an artificial skin composed of two layers: collagen and a poly-alpha-amino acid. Berg et al. (U.S. patent application Ser. No. 4,841,962, issued Jun. 27, 1989), disclosed a wound dressing composed of three layers: an adhesive, a cross-linked collagen matrix, and a multilayer polymer film. Holman, U.S. Pat. No. 4,950,699, issued Aug. 21, 1990, disclosed a wound dressing consisting of less than 10% collagen mixed with an acrylic adhesive. Cioca et al., British Patent 1,347,582, disclosed a collagenic wound dressing consisting of a freeze dried polydisperse collagen mixture.
Steffan et al., European Patent Application 069260, published Jan. 12, 1983, disclosed a collagen insert consisting of high purity native collagen. Zimmerman et al. (U.S. Pat. No. 4,453,939, issued Jun. 12, 1984), disclosed a wound healing composition containing collagen coated with fibrinogen, factor XIII fibrinigen, and/or thrombin. Leibovich et al. (U.S. Pat. No. 4,808,402, issued February 1989), disclosed a composition for treating wounds comprising collagen, bioerodible polymer, and tumor necrosis factor. Yannas and Burke (J. Biomed. Mat. Res. 14:68-81 (1980)), have reviewed the design of artificial skin, some examples of which contain collagen. Chvapil et al., Int. Rev. Connect. Tissue Res. 6:1-61 (1973), particularly at pages 51 to 52; and Pachence et al., Med. Device and Diag. Ind., 9:49-55 (1987), disclose various uses of collagen, including its use as a drug delivery vehicle.
Most of the previously utilized collagen containing sponges have been used as substrates or skeletons for the growth of cells at a wound site and have not been used for the delivery of pharmaceutical agents. The present invention provides a much desired improvement in pharmaceutical sponges by providing for a steady, continuous and sustained release of therapeutic agents over an extended period of time.